CTSK variant implicated in suspected pyknodysostosis in a domestic cat

Abstract

Case summary A 9-month-old entire male domestic longhair cat presented with a history of pathological fractures, chronic musculoskeletal pain and poor growth. Multiple facial and skeletal abnormalities were identified on physical examination and advanced imaging (CT and radiographs). A variant in CTSK was identified in the affected cat following whole-exome sequencing (WES). The cat was managed symptomatically with diet, environmental modifications and analgesia. Relevance and novel information This is the first report of a cat with a similar clinical presentation and genetic variant to the hereditary human genetic disorder pyknodysostosis. In this case, WES was performed, which often facilitates the diagnosis of various hereditary disorders (ie, a conceptual framework for practicing feline genomic medicine). Despite the severe skeletal and appendicular abnormalities described, the cat was alive more than 2 years after its initial presentation.

Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X‐linked muscular dystrophy in a cat

“…Specific tools from GATK 4.2 for genotyping, variant database construction, and hard‐filtering were completed as previously described 32 . The produced 22 cat dataset was combined with the previously produced 340 cat variant call file 24,32,33 and the 61 cat WES dataset for the 99 Lives Cat Genome Sequencing Initiative 34‐36 . The National Center for Biotechnology Information (NCBI) RefSeq Felis catus annotation 104 and Ensembl Variant Effect Predictor 37 were used to characterize the variants.…”

“… 32 The produced 22 cat dataset was combined with the previously produced 340 cat variant call file 24 , 32 , 33 and the 61 cat WES dataset for the 99 Lives Cat Genome Sequencing Initiative. 34 , 35 , 36 The National Center for Biotechnology Information (NCBI) RefSeq Felis catus annotation 104 and Ensembl Variant Effect Predictor 37 were used to characterize the variants. Exonic variants and 10 bp flanking each exon were filtered and visualized using VarSeq software (GoldenHelix, Bozeman, Montana).…”